Objective-Inflammation plays a key role in atherosclerosis. We hypothesized that novel inflammatory markers may predict the risk of coronary heart disease (CHD).Approach and Results-We investigated the association of 16 inflammatory biomarkers with the risk of CHD in a random subset of 839 CHD-free individuals in a prospective population-based cohort study. A Bonferroni corrected P value of 3.1×10-3 was used as a threshold of statistical significance. The mean age at baseline was 72.8 years. During a median follow-up of 10.6 years, 99 cases of incident CHD were observed. Among all inflammatory biomarkers, neutrophilderived human s100a12 (extracellular newly identified receptor for advanced glycation end-products binding protein [EN-RAGE]) showed the strongest association with the risk of CHD (P value 2.0×10-3). After multivariable adjustment for established cardiovascular risk factors, each standard deviation increase in the natural log-transformed EN-RAGE was associated with 30% higher risk of incident CHD (hazard ratio, 1.30; 95% confidence interval, 1.06-1.59). Further adjustment for previously studied inflammatory markers did not attenuate the association. Excluding individuals with prevalent type 2 diabetes mellitus, impaired kidney function, or individuals using antihypertensive medication did not change the effect estimates. Cause-specific hazard ratios suggested a stronger association between EN-RAGE and CHD mortality compared with stable CHD.Conclusions-Our results highlight EN-RAGE as an inflammatory marker for future CHD in a general population, beyond traditional CHD risk factors and inflammatory markers.

Additional Metadata
Keywords Biomarker, Coronary artery disease, Cytokines, Inflammation
Persistent URL dx.doi.org/10.1161/ATVBAHA.114.304306, hdl.handle.net/1765/82886
Journal Arteriosclerosis, Thrombosis, and Vascular Biology
Citation
Ligthart, S, Sedaghat, S, Ikram, M.A, Hofman, A, Franco, O.H, & Dehghan, A. (2014). A novel inflammatory marker for incident coronary heart disease. Arteriosclerosis, Thrombosis, and Vascular Biology, 34(12), 2695–2699. doi:10.1161/ATVBAHA.114.304306